CLEARANCE STUDIES OF OXYTOCIN IN HUMANS USING RADIOIMMUNOASSAY MEASUREMENTS OF THE HORMONE IN PLASMA AND URINE

Synthetic oxytocin (OT) was infused Iv in four men at 3 mU/min, and the rate was doubled every 90 min for a total of three infusion periods. The mean ( .+-. SEM) OT MCR was 16.4 .+-. 1.7 ml/kg .cntdot. min and was independent of the rate of infusion. A method for measuring OT in urine was developed using an octadecasilyl-silica column for extraction of the hormone. The extracted residue was reconstituted in potassium phosphate buffer, pH 7.4, for RIA. The minimum detectable level of OT in urine was 0.2 .mu.U/ml (defined as a bound to free ratio of .apprx. 90%). The mean recovery of OT was 77 .+-. 2%. The mean ( .+-. SEM) concentration of endogenous OT in urine was 10.2 .+-. 1.4 .mu.U/ml. Endogenous OT in urine eluted from a reverse phase high pressure liquid chromatography column as a single peak of OT immunoreactivity in the position of synthetic OT. Urinary OT excretion during infusion of synthetic OT was linearly correlated with plasma OT concentration whether calculated as microunits of urinary OT per mg creatinine (r = 0.89) or urinary OT per min (r = 0.93). Mean urinary fractional clearance of OT (OT clearance/creatinine clearance) was 3.6% renal clearance of OT (5.5 ml/min or 0.43% of MCR). Thus, OT MCR was constant over a wide range of physiological plasma OT levels and was similar to MCR in pregnant women studied previously in this laboratory. Less than 1% of OT was cleared in urine. This study defines the relationship between urinary and plasma OT during steady state infusion of physiological concentrations of the hormone and indicates that measurements of OT in urine by RIA may prove helpful for pharmacokinetic and physiological studies of OT-related events in humans.